Search PubMed⌕ Search

Biomedical subjects

J Swenson

Publications and source records attributed to J Swenson.

33 records · Page 2Linked to original sources

Comparison of the positional cloning methods used to isolate the BRCA1 gene.

A critical step in positional cloning is the identification of candidate genes from a large, genetically defined region. Candidate gene isolation by hybrid selection, genomic sequencing, and direct cDNA library screening identified 45 candidate gene fragments (CGFs) from a 600 kb genomic region that contains the BRCA1 gene. These CGFs define a minimum of 15 genes, six of which are newly localized to the BRCA1 region. We present an analysis of the efficiency and the sequences generated for each of these methods. We also compare our CGF set to those reported for the BRCA1 region by three other groups, revealing a surprising lack of overlap among the sets.

Breast Neoplasms↗

Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture.

Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study.

Amino Acid Sequence↗

Ability of clinical laboratories to detect antimicrobial agent-resistant enterococci.

To test the ability of clinical laboratories to detect antimicrobial resistance among enterococci, we sent four vancomycin-resistant enterococcal strains and one beta-lactamase-producing enterococcus to all 93 nongovernment, hospital-based clinical laboratories in New Jersey; 76 (82%) participated in the study. Each organism was tested by the laboratory's routine antimicrobial susceptibility testing method. The proportion of laboratories that correctly reported that an isolate was resistant to vancomycin varied according to the resistance level of the isolate: high-level resistance (MIC for Enterococcus faecium = 512 micrograms/ml), 96% of laboratories correct; moderate-level resistance (MIC for E. faecium = 64 micrograms/ml), 27% correct; low-level resistance (MIC for Enterococcus faecalis = 32 micrograms/ml), 16% correct; and intrinsic low-level resistance (MIC for Enterococcus gallinarum = 8 micrograms/ml), 74% correct. The beta-lactamase-producing E. faecalis isolate was identified as resistant to penicillin and ampicillin by 66 and 8% of laboratories, respectively, but only three laboratories recognized that it was a beta-lactamase producer. This survey suggests that many laboratories may fail to detect antimicrobial agent-resistant enterococci.

Ampicillin Resistance↗

Patterns and mechanisms of beta-lactam resistance among isolates of Escherichia coli from hospitals in the United States.

To study the national distribution of beta-lactam resistance patterns and mechanisms among Escherichia coli organisms isolated in U.S. hospitals, 652 ampicillin-resistant (Am(r)) or ampicillin-intermediate (Ami) isolates were submitted to the Centers for Disease Control from March 1983 through July 1984 by nine hospitals participating in the National Nosocomial Infections Study. Among the isolates (most of which caused urinary tract infections), 78% were Am(r) and 22% were Ami by the interpretative criteria established by the National Committee for Clinical Laboratory Standards. Resistance to carboxypenicillins ranged from 73 to 74%, and that to acylureidopenicillins ranged from 43 to 66%. A total of 26% of the isolates were resistant to cephalothin, and 4% were resistant to cefazolin. Resistance to cefoxitin was 1%, while resistances to cefuroxime and cefamandole were 2 and 7%, respectively. With the exception of cefsulodin (98% resistant) and cefoperazone (1% resistant), there was no resistance to newer cephalosporins or aztreonam. In general, only minor differences in the incidence of resistance to beta-lactam antibiotics were noted in hospital-acquired versus non-hospital-acquired isolates as well as among isolates from various regions of the United States. TEM beta-lactamases were produced by 87% of the 237 Am(r) isolates examined. By our methods, OXA and chromosomal (type I) beta-lactamases were detected in 2 and 28 isolates, respectively, and plasmid-mediated extended-spectrum cephalosporinases were detected in none of the isolates. Disk substrate and clavulanic acid inhibition assays revealed that TEM beta-lactamase conferred Am(r) and resistance to carboxypenicillins, acylureidopenicillins, cephalothin, cefamandole, cefsulodin, and cefoperazone. A total of 391 isolates were screened for plasmids, and 259 isolates were examined by DNA hybridization with a TEM probe. Among 462 plasmids probed, 129 plasmids, ranging from 4 to 140 megadaltons, harbored TEM sequences. Although beta-lactam resistance in clinical isolates of E. coli is predominantly mediated by TEM beta-lactamase, the diverse spectrum of resistance appears to be related to additional strain=dependent factors.

Ampicillin↗

Mechanical and bone ingrowth properties of a polymer-coated, porous, synthetic, coralline hydroxyapatite bone-graft material.

CHAG, that is, porous hydroxyapatite hydrothermally converted from the calcium carbonate exoskeleton of a coral (genus Goniopora), has been shown to be effective as a scaffold for bone ingrowth. The large pores in the material, however, resulted in low compressive strengths. Compressive testing was performed to assess the changes in mechanical properties by coating the internal surfaces of CHAG with DL-PLA. Plugs of CHAG with thick (3:1 chloroform to DL-PLA by weight), medium (10:1), and thin (30:1) coatings as well as uncoated CHAG were then implanted transcortically in the proximal third of the diaphysis of rabbit tibiae to assess the in vivo response. The mechanical tests demonstrated significantly improved compressive strength, stiffness, and energy absorption for coated specimens compared with uncoated specimens. Coated specimens were not significantly different from canine tibial cancellous bone in strength and stiffness although they achieved only 36% of the energy absorption capacity. Specimens from rabbit tibiae were harvested at 3, 12, and 24 weeks for interface shear strength determination and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa compared with 17 MPa for specimens with 30:1 coatings and 8 MPa for specimens with 10:1 and 3:1 coatings. At 24 weeks, there were no significant differences in shear stress between any of the specimens. Histomorphometric assessments showed that the ratio of area fraction of new bone to area fraction of new bone and void space increased from 68-70% for specimens with 3:1 and 10:1 coatings at 3 weeks to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating.

Animals↗

Bone ingrowth into polymer coated porous synthetic coralline hydroxyapatite.

Porous hydroxyapatite, converted hydrothermally from the calcium carbon exoskeleton of the coral genus Goniopora (CHAG), has been shown to be effective as a scaffold for bone ingrowth (2,3,5-7,9). However, the large pores in the material resulted in low compressive strengths. In a previous study, we found that microcoating the internal surfaces of CHAG with dilactic-polyactic acid (DL-PLA) improved significantly its compressive properties. The objective of this study was to determine the effect of PLA microcoating on bone ingrowth into CHAG plugs. Plugs of thick- (3:1 chloroform to DL-PLA by weight), medium- (10:1), and thin- (30:1) coated as well as uncoated CHAG were implanted transcortically in the proximal third of the diaphysis of the rabbit tibia. Specimens were harvested at 3, 12, and 24 weeks for mechanical testing and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa, compared with 17 MPa for 30:1 and 8 MPa for 10:1 and 3:1 coated specimens. At 24 weeks, there were no significant differences in shear stress among any of the specimens. Histomorphometric assessments showed that the ratio of area fractions of new bone to area fractions of new bone and void space increased from 68-70% for 3:1 and 10:1 coated specimens at 3 weeks, and to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating.

Animals↗

Decontamination of urinary bags for rehabilitation patients.

Patients with neurologic injuries frequently have permanent indwelling or external catheters connected to disposable urinary bags. These patients routinely disconnect the bed bag during the day and apply a leg bag which can be concealed under their clothes. In our rehabilitation unit, both bags are discarded daily. This study investigated the possibility of safely reusing bed and leg bags. The procedure involved decontamination of the bags using 180 ml of a 1% solution of sodium hypochlorite. Initially, discarded bed and leg bags were decontaminated in the lab to ensure effectiveness of the procedure. Next, 22 patients reused their bed and leg bags with daily decontamination by the rehabilitation nursing staff. These bags were reused for two to eight days. Cultures of 137 bags were obtained to evaluate the technique. All cultures were negative. Baseline urine cultures for both time periods showed no significant difference in rates of bacteriuria. The potential savings for one year on our rehabilitation unit, with an average of 12 catheterized patients, would be approximately $39,000. Although this methodology conflicts with thoughts about not reusing disposable products, we have shown that the procedure can be done safely in rehabilitation patients and it is easy and inexpensive.

Bacteriuria↗

Wrist driven flexor hinge orthosis: linkage design improvements.

Wrist driven flexor hinge orthosis (WDFHO) linkage movements were analyzed graphically for existing kit form orthoses and modified orthoses. The graphical analysis indicated improved function by increased torque and resultant pinch force in modified orthoses. A geometric solution to pivot point location which will allow clinicians and orthotists to properly locate the linkage pivot points for WDFHOs was developed. Improved function was documented in 5 orthoses converted from kit form linkages to modified linkages.

Hand↗